Group 1 metabotropic glutamate receptor 5 is involved in synaptically-induced Ca2+-spikes and cell death in cultured rat hippocampal neurons.

Group 1 metabotropic glutamate receptors (mGluRs) can positively affect postsynaptic neuronal excitability and epileptogenesis. The objective of the present study was to determine whether group 1 mGluRs might be involved in synaptically-induced intracellular free Ca2+ concentration ([Ca2+]i) spikes and neuronal cell death induced by 0.1 mM Mg2+ and 10 µM glycine in cultured rat hippocampal neurons from embryonic day 17 fetal Sprague-Dawley rats using imaging methods for Ca2+ and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays for cell survival. Reduction of extracellular Mg2+ concentration ([Mg2+]o) to 0.1 mM induced repetitive [Ca2+]i spikes within 30 sec at day 11.5. The mGluR5 antagonist 6-Methyl-2-(phenylethynyl) pyridine (MPEP) almost completely inhibited the [Ca2+]i spikes, but the mGluR1 antagonist LY367385 did not. The group 1 mGluRs agonist, 3,5-dihydroxyphenylglycine (DHPG), significantly increased the [Ca2+]i spikes. The phospholipase C inhibitor U73122 significantly inhibited the [Ca2+]i spikes in the absence or presence of DHPG. The IP3 receptor antagonist 2-aminoethoxydiphenyl borate or the ryanodine receptor antagonist 8-(diethylamino)octyl 3,4,5-trimethoxybenzoate also significantly inhibited the [Ca2+]i spikes in the absence or presence of DHPG. The TRPC channel inhibitors SKF96365 and flufenamic acid significantly inhibited the [Ca2+]i spikes in the absence or presence of DHPG. The mGluR5 antagonist MPEP significantly increased the neuronal cell survival, but mGluR1 antagonist LY367385 did not. These results suggest a possibility that mGluR5 is involved in synaptically-induced [Ca2+]i spikes and neuronal cell death in cultured rat hippocampal neurons by releasing Ca2+ from IP3 and ryanodine-sensitive intracellular stores and activating TRPC channels.

Risk Factors for Intravenous Propacetamol-Induced Blood Pressure Drop in the Neurointensive Care Unit: A Retrospective Observational Study.

BACKGROUND: Intravenous propacetamol is commonly used to control fever and pain in neurocritically ill patients in whom oral administration is often difficult. However, several studies reported that intravenous propacetamol may cause blood pressure drop. Thus, we aimed to investigate the occurrence and risk factors for intravenous propacetamol-induced blood pressure drop in neurocritically ill patients. METHODS: This retrospective study included consecutive patients who were administered intravenous propacetamol in a neurointensive care unit at a single tertiary academic hospital between April 2013 and June 2020. The exact timing of intravenous propacetamol administration was collected from a database of the electronic barcode medication administration system. Blood pressure drop was defined as a systolic blood pressure below 90 mm Hg or a decrease by 30 mm Hg or more. Blood pressure, pulse rate, and body temperature were collected at baseline and within 2 h after intravenous propacetamol administration. The incidence of blood pressure drop was evaluated, and multivariable logistic regression analysis was performed to identify risk factors for blood pressure drop events. RESULTS: A total of 16,586 instances of intravenous propacetamol administration in 4916 patients were eligible for this study. Intravenous propacetamol resulted in a significant decrease in systolic blood pressure (baseline 131.1 ± 17.8 mm Hg; within 1 h 124.6 ± 17.3 mm Hg; between 1 and 2 h 123.4 ± 17.4 mm Hg; P < 0.01). The incidence of blood pressure drop events was 13.5% within 2 h after intravenous propacetamol. Older age, lower or higher baseline systolic blood pressure, fever, higher Acute Physiology and Chronic Health Evaluation II score, and concomitant administration of vasopressors/inotropes or analgesics/sedatives were significant factors associated with the occurrence of blood pressure drop events after intravenous propacetamol administration. CONCLUSIONS: Intravenous propacetamol can induce hemodynamic changes and blood pressure drop events in neurocritically ill patients. This study identified the risk factors for blood pressure drop events. On the basis of our results, judicious use of intravenous propacetamol is warranted for neurocritically ill patients with risk factors that make them more susceptible to hemodynamic changes.

Intravenous Fluid Selection for Unruptured Intracranial Aneurysm Clipping : Balanced Crystalloid versus Normal Saline.

OBJECTIVE: While balanced crystalloid (BC) could be a relevant fluid regimen with buffer system compared with normal saline (NS), there have been no studies on the optimal fluid for surgery of an unruptured intracranial aneurysm (UIA). This study aimed to compare the effects of fluid regimens between NS and BC on the metabolic and clinical outcomes of patients who underwent surgery for UIA. METHODS: This study was designed as a propensity score matched retrospective comparative study and included adult patients who underwent UIA clipping. Patient groups were categorized as NS and BC groups based on the types of pre-operative fluid and the amount of fluid administered during surgery. The primary outcomes were defined as electrolyte imbalance and acidosis immediately after surgery. The secondary outcomes were the length of stay in the intensive care unit (ICU) and duration from the end of the operation to extubation. RESULTS: A total of 586 patients were enrolled in this study, with each of 293 patients assigned to the NS and BC groups, respectively. Immediately after surgery, serum chloride levels were significantly higher in the NS group. Compared to the NS group, the BC group had lower incidence rates of acidemia (6.5% vs. 11.6%, p=0.043) and metabolic acidosis (0.7% vs. 4.4%, p=0.007). As compared to NS group, BC group had significantly shorter duration from the end of the operation to extubation (250±824 vs. 122±372 minutes, p=0.016) and length of stay in ICU (1.37±1.11 vs. 1.12±0.61 days, p=0.001). Throughout multivariable analysis, use of BC was found to be significant factor for favorable post-operative results. CONCLUSION: This study showed that the patients who received BC during UIA clipping had lower incidence of metabolic acidosis, earlier extubation and shorter ICU stay compared to those who received NS. Therefore, using BC as a peri-operative fluid can be recommended for patients who undergo surgery for UIA.

A comparative study on patient safety attitude between nurses and doctors in operating rooms.

OBJECTIVE: To investigate and compare the attitudes of operating room nurses and doctors regarding patient safety, performance of surgical time-out and recognition of count error. METHODS: This cross-sectional study recruited operating room nurses, surgeons and anaesthesiologists between 1 August 2015 and 5 February 2016. A Safety Attitude Questionnaire was used to analyse the three elements in both groups of operating room staff (nurses and doctors). RESULTS: The study analysed the questionnaires from 171 participants; 95 nurses (55.6%) and 76 doctors (44.4%). Differences exist between doctors and nurses regarding teamwork climate, working conditions, perception of management and the recognition of stress. On the performance of surgical time-out, nurses showed higher scores on way of counting, while doctors showed higher scores on the time-out procedure itself. Also, doctors believed they actively cooperated with the nurses, while nurses believed they did not receive cooperation. Scores for the recognition of count error were higher in nurses than in doctors. More experienced operating room staff showed higher scores than younger less experienced staff. CONCLUSIONS: Perceptual differences among doctors and nurses need to be minimized for the safety of the patient in the operating room.

Cyanidin-3-glucoside inhibits amyloid ß25-35-induced neuronal cell death in cultured rat hippocampal neurons.

Increasing evidence implicates changes in [Ca2+]i and oxidative stress as causative factors in amyloid beta (Aß)-induced neuronal cell death. Cyanidin-3-glucoside (C3G), a component of anthocyanin, has been reported to protect against glutamate-induced neuronal cell death by inhibiting Ca2+ and Zn2+ signaling. The present study aimed to determine whether C3G exerts a protective effect against Aß25-35-induced neuronal cell death in cultured rat hippocampal neurons from embryonic day 17 fetal Sprague-Dawley rats using MTT assay for cell survival, and caspase-3 assay and digital imaging methods for Ca2+, Zn2+, MMP and ROS. Treatment with Aß25-35 (20 µM) for 48 h induced neuronal cell death in cultured rat pure hippocampal neurons. Treatment with C3G for 48 h significantly increased cell survival. Pretreatment with C3G for 30 min significantly inhibited Aß25-35-induced [Zn2+]i increases as well as [Ca2+]i increases in the cultured rat hippocampal neurons. C3G also significantly inhibited Aß25-35-induced mitochondrial depolarization. C3G also blocked the Aß25-35-induced formation of ROS. In addition, C3G significantly inhibited the Aß25-35-induced activation of caspase-3. These results suggest that cyanidin-3-glucoside protects against amyloid ß-induced neuronal cell death by reducing multiple apoptotic signals.

Protective effects of PEP-1-Catalase on stress-induced cellular toxicity and MPTP-induced Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disability caused by a decrease of dopaminergic neurons in the substantia nigra (SN). Although the etiology of PD is not clear, oxidative stress is believed to lead to PD. Catalase is antioxidant enzyme which plays an active role in cells as a reactive oxygen species (ROS) scavenger. Thus, we investigated whether PEP-1-Catalase protects against 1-methyl-4-phenylpyridinium (MPP+) induced SH-SY5Y neuronal cell death and in a 1-methyl- 4-phenyl-1,2,3,6-trtrahydropyridine (MPTP) induced PD animal model. PEP-1-Catalase transduced into SH-SY5Y cells significantly protecting them against MPP+-induced death by decreasing ROS and regulating cellular survival signals including Akt, Bax, Bcl-2, and p38. Immunohistochemical analysis showed that transduced PEP-1-Catalase markedly protected against neuronal cell death in the SN in the PD animal model. Our results indicate that PEP-1-Catalase may have potential as a therapeutic agent for PD and other oxidative stress related diseases.